The purpose of this study was to assess the follow-up of patients with vaccinia-associated myocarditis. With the threat of biological warfare, the U.S. Department of Defense resumed a program for widespread smallpox vaccinations on December 13, 2002. One-year afterwards, there has been a significant increase in the occurrence of myocarditis and pericarditis among those vaccinated. Cases were identified through sentinel reporting to military headquarters, systematic surveillance, and spontaneous reports. A total of 540,824 military personnel were vaccinated with a New York City Board of Health strain of vaccinia from December 2002 through December 2003. Of these, 67 developed myopericarditis at 10.4 3.6 days after vaccination. The ST-segment elevation was noted in 57%, mean troponin on admission was 11.3 +/- 22.7 ng/dl, and peak cardiac enzymes were noted within 8 h of presentation. On follow-up of 64 patients (96%) at a mean of 32 16 weeks, all patients had objective normalization of echocardiography, electrocardiography, laboratory testing, graded exercise testing, and functional status; 8 (13%) reported atypical, non-limiting persistent chest discomfort. Post-vaccinial myopericarditis should be considered in patients with chest pain within 30 days after smallpox vaccination. Normalization of echocardiography, electrocardiography, and treadmill testing is expected, and nearly all patients have resolution of chest pain on follow-up.